7ZZU

Inhibitory Ligand binding to HDAC2

7ZZU の概要

• エントリーDOI: 10.2210/pdb7zzu/pdb
• 分子名称: Histone deacetylase 2, 1,2-ETHANEDIOL, TETRAETHYLENE GLYCOL, ... (10 entities in total)
• 機能のキーワード: protein deacetylation, transcriptional repressor complex, chromatin binding, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 172941.68

構造登録者

Cleasby, A.,Tisi, D. (登録日: 2022-05-26, 公開日: 2022-09-21, 最終更新日: 2024-06-19)

主引用文献

Tamanini, E.,Miyamura, S.,Buck, I.M.,Cons, B.D.,Dawson, L.,East, C.,Futamura, T.,Goto, S.,Griffiths-Jones, C.,Hashimoto, T.,Heightman, T.D.,Ishikawa, S.,Ito, H.,Kaneko, Y.,Kawato, T.,Kondo, K.,Kurihara, N.,McCarthy, J.M.,Mori, Y.,Nagase, T.,Nakaishi, Y.,Reeks, J.,Sato, A.,Schopf, P.,Tai, K.,Tamai, T.,Tisi, D.,Woolford, A.J.
Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor.
Acs Med.Chem.Lett., 13:1591-1597, 2022

PubMed Abstract: Fragment-based ligand discovery was successfully applied to histone deacetylase HDAC2. In addition to the anticipated hydroxamic acid- and benzamide-based fragment screening hits, a low affinity (∼1 mM) α-amino-amide zinc binding fragment was identified, as well as fragments binding to other regions of the catalytic site. This alternative zinc-binding fragment was further optimized, guided by the structural information from protein-ligand complex X-ray structures, into a sub-μM, brain penetrant, HDAC2 inhibitor () capable of modulating histone acetylation levels .

PubMed: 36262388
DOI: 10.1021/acsmedchemlett.2c00272

実験手法

X-RAY DIFFRACTION (1.85 Å)